Summary |
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Variant origin |
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Variant description |
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Phenotypes |
View phenotypes and curated references for all genotypes (concatenated display).
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Notes |
Lore5 exhibits an additive mode of inheritance.
Candidate Genes
Candidate genes for ethanol sensitivity QTL Lore1 (loss of righting induced by ethanol 1), Lore2, Lore4, and Lore5 were identified using Affymetrix gene microarray analysis. RNA from the cerebella of male animals from inbred strains LS and SS were hybridized to 2 different sets of Affymetrix gene chips and analyzed for gene expression differences. The inbred strain LS exhibits increased alcohol sensitivity compared to SS. A total of 15 candidate genes were identified, 4 of which have polymorphisms between LS and SS. Mapping and Phenotype information for this QTL, its variants and associated markersJ:38534A large (LSxSS)F2 intercross was used to confirm QTLs involved in ethanol-induced sleep time and identify new QTLs. The LS (long sleep) inbred strain sleeps an average of 2 hours when administered an intraperitoneal ethanol injection. In contrast, the SS(short sleep) inbred strain sleeps an average of 10 minutes when administered an intraperitoneal ethanol injection. Lore1, previously identified in 27 LSxSS RI (recombinant inbred) strains (Bennett, J:40119), was confirmed in this study on mouse chromosome 1 spanning 43 cM - 59 cM (peak LOD = 5.4 at 54 cM). Possible candidate genes in this region are Chrnd (Acrd-acetylcholine receptor subunit delta) and Chrng (Acrg-acetylcholine receptor subunit gamma) at 52.3 cM. Lore2 on chromosome 2 spanning 78 cM - 95 cM (peak LOD = 6.6 at 85 cM) was also confirmed. A possible candidate gene for Lore2 is Ntsr at 107 cM on chromosome 2. New QTLs Lore3 (chromosome 8 spanning 44 cM - 71 cM, peak LOD = 3.4 at 59 cM), Lore4 (chromosome 11 spanning 44 cM - 56 cM, peak LOD = 6.5 at 49 cM), and Lore5 (chromosome 15 spanning 32 cM - 55 cM, peak LOD = 4.0 at 46 cM) were mapped. Suggestive QTLs Lore6 mapped to chromosome 18 (spanning 24 cM - tel, peak LOD = 1.8 at 41 cM) and Lore7 mapped to chromosome 7 (spanning 25 cM - 61 cM,peak LOD = 1.7 at 50 cM). Lore1 - Lore7 are inherited in an additive fashion. Lore1, Lore2, Lore4, and Lore5 map near QTLs associated with NT (neurotensin) receptor density. No evidence of epistasis between Lore1 - Lore7 was detected. Loci associated with blood ethanol concentration (BEC) were also analyzed in the (LSxSS)F2 population. SS mice wake with higher BEC than LS mice. 6 putative BEC QTLs (LOD = 2.0 - 3.0) were identified on chromosomes 2, 8, 9, 22, 14, and 15, and will be further analyzed for confirmation. J:52088Authors construct several lines of speed congenics using the QMACS (QTL-Marker-Assisted Counter Selection) strategy to confirm previously mapped QTLs associated with hypnotic sensitivity to ethanol (Markel, J:38534). Each Lore QTL was separately backcrossed onto either the inbred short sleep (ISS) background or the inbred long sleep background (ILS) for 6-8 generations. Lore1, Lore2, Lore4, and Lore5 were confirmed using this strategy. Lore3, a suggestive QTL, appears to have been lost. Significance scores for each congenic line Lore QTL are as follows: Lore1 on mouse chromosome 1 at 54 cM, P = 0.01; Lore2 on mouse chromosome 2 at 85 cM, P = 0.006; Lore4 on mouse chromosome 11 at 49 cM, P = 0.0008; and Lore5 on mouse chromosome 15 at 46 cM, P = 0.003. J:151159A multistage mapping strategy involving Long sleep (LS) and short-sleep (SS) mice was employed to refine the QTL mapping of Lore1, Lore2, Lore4 and Lore5. ( see Table 1 of text) Using 39 progeny from ISCS (Interval-specific congenic strains) lines 11, 4and 13 the mapping of Lore1 was refined to a region of mouse Chromosome 1 bounded by D1Mit180 and D1Mit192.Using 79 progeny from ISCS (Interval-specific congenic strains) lines 10, 14, 2 and 5 the mapping of Lore2 was refined to a region of mouse Chromosome 2 bounded by D2Mit403 and D2Mit457.Using 24 progeny from ISCS (Interval-specific congenic strains) lines 9 and 1 the mapping of Lore4 was refined to a region of mouse Chromosome 11 bounded by D11Mit40 and D11Mit258.Using 38 progeny from ISCS (Interval-specific congenic strains) lines 2 and 11 the mapping of Lore5 was refined to a region of mouse Chromosome 15 bounded by D15Mit84 and D15Mit121.The evidence for these mappings are shown figuratively in figs 2-5 of the text. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 10/29/2024 MGI 6.24 |
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